Histone Deacetylase 1 Down-Regulation on Developmental Capability and Histone Acetylation in Bovine Oocytes and Parthenogenetic Embryos

2011 ◽  
Vol 46 (6) ◽  
pp. 1022-1028 ◽  
Author(s):  
Z Wang ◽  
T Zhao ◽  
P Zhang ◽  
S Zhang ◽  
J Guan ◽  
...  
2016 ◽  
Vol 37 (5) ◽  
pp. 321-327 ◽  
Author(s):  
Brenda J. Curtis ◽  
Jill A. Shults ◽  
Luis Ramirez ◽  
Elizabeth J. Kovacs

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 652-658 ◽  
Author(s):  
Jennifer L. Aron ◽  
Mark R. Parthun ◽  
Guido Marcucci ◽  
Shinichi Kitada ◽  
Andrew P. Mone ◽  
...  

AbstractDepsipeptide is in clinical trials for chronic lymphocytic leukemia (CLL) on the basis of earlier observations demonstrating selective in vitro activity in CLL. We sought to determine the relationship of histone H3 and H4 acetylation, inhibition of histone deacetylase, and apoptosis observed in CLL cells to justify a pharmacodynamic end point in these clinical trials. We demonstrate that in vitro depsipeptide induces histone H3 and H4 acetylation and histone deacetylase enzyme inhibition at concentrations corresponding to the LC50 (concentration producing 50% cell death) for cultured CLL cells (0.038 μM depsipeptide). The changes in histone acetylation are lysine specific, involving H4 K5, H4 K12, and H3 K9, and to a lesser extent H4 K8, but not H4 K16 or H3 K14. Depsipeptide-induced apoptosis is caspase dependent, selectively involving the tumor necrosis factor (TNF) receptor (extrinsic pathway) initiating caspase 8 and effector caspase 3. Activation of caspase 8 was accompanied by the down-regulation of cellular FLICE-inhibitory protein (c-FLIP, I-FLICE) without evidence of Fas (CD95) up-regulation. Changes in other apoptotic proteins, including Bcl-2, Bax, Mcl-1, and X-linked inhibitor of apoptosis (XIAP), were not observed. Our results demonstrate a relationship between target enzyme inhibition of histone deacetylase, histone H3 and H4 acetylation, and apoptosis involving the TNF-receptor pathway of apoptosis that is not used by other therapeutic agents in CLL. These data suggest use of histone H3 and H4 acetylation, inhibition of histone deacetylase, and down-regulation of FLIP as pharmacodynamic end points for further evaluation of this drug in patients.


2021 ◽  
Vol 22 (9) ◽  
pp. 4477
Author(s):  
Hye Sun Shin ◽  
Yuri Lee ◽  
Mi Hee Shin ◽  
Soo Ick Cho ◽  
Christos C. Zouboulis ◽  
...  

Proper regulation of sebum production is important for maintaining skin homeostasis in humans. However, little is known about the role of epigenetic regulation in sebocyte lipogenesis. We investigated histone acetylation changes and their role in key lipogenic gene regulation during sebocyte lipogenesis using the human sebaceous gland cell line SZ95. Sebocyte lipogenesis is associated with a significant increase in histone acetylation. Treatment with anacardic acid (AA), a p300 histone acetyltransferase inhibitor, significantly decreased the lipid droplet number and the expression of key lipogenic genes, including sterol regulatory-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). In contrast, treatment with trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, increased the expression of these genes. Global HDAC enzyme activity was decreased, and HDAC1 and HDAC2 expression was downregulated during sebaceous lipogenesis. Interestingly, HDAC1 knockdown increased lipogenesis through SREBP1 induction, whereas HDAC1 overexpression decreased lipogenesis and significantly suppressed SREBP1 promoter activity. HDAC1 and SREBP1 levels were inversely correlated in human skin sebaceous glands as demonstrated in immunofluorescence images. In conclusion, HDAC1 plays a critical role in reducing SREBP1 transcription, leading to decreased sebaceous lipogenesis. Therefore, HDAC1 activation could be an effective therapeutic strategy for skin diseases related to excessive sebum production.


2011 ◽  
Vol 104 (2) ◽  
pp. 312-320 ◽  
Author(s):  
Lydia Miller ◽  
Chad D. Foradori ◽  
Avin S. Lalmansingh ◽  
Dharmendra Sharma ◽  
Robert J. Handa ◽  
...  

2020 ◽  
Vol 32 (7) ◽  
pp. 690
Author(s):  
Thais P. Pontelo ◽  
Sarah A. D. Rodrigues ◽  
Taynan S. Kawamoto ◽  
Ligiane O. Leme ◽  
A. C. M. M. Gomes ◽  
...  

We aimed to analyse the histone acetylation status and expression profile of genes involved in histone acetylation (histone acetyltransferase 1 (HAT1), lysine acetyltransferase 2A (KAT2A), histone deacetylase 1(HDAC1), HDAC2 and HDAC3) in bovine oocytes of different competences during invitro maturation (IVM). Cumulus–oocyte complexes were recovered from two groups of follicles: minor follicles (1.0–3.0mm in diameter), classified as low competence (LC) and large follicles (6.0–8.0mm in diameter) classified as high competence (HC). Oocytes were submitted to IVM for 0, 8 and 24h and stored for analysis. Acetylation status of histone H4 on lysine K5, K6, K12 and K16 was assessed by immunohistochemistry. For gene expression, mRNA levels were determined by real-time quantitative polymerase chain reaction. All oocytes, regardless of their competence, showed a gradual decrease (P<0.05) in acetylation signals during IVM. From 0 to 8h of maturation, an increase (P<0.05) in the relative abundance of HAT1 mRNA was observed only in the HC oocytes. In this group, higher (P<0.05) mRNA levels of HDAC1 at 8h of maturation were also observed. In conclusion, in the present study, LC oocytes were shown to have adequate acetylation levels for the resumption and progression of meiosis; however, these oocytes do not have the capacity to synthesise RNA during IVM as the HC oocytes do.


Genetics ◽  
2003 ◽  
Vol 165 (1) ◽  
pp. 399-409 ◽  
Author(s):  
Lu Tian ◽  
Jianlin Wang ◽  
M Paulus Fong ◽  
Meng Chen ◽  
Hongbin Cao ◽  
...  

Abstract Little is known about the role of genetic and epigenetic control in the spatial and temporal regulation of plant development. Overexpressing antisense Arabidopsis thaliana HD1 (AtHD1) encoding a putative major histone deacetylase induces pleiotropic effects on plant growth and development. It is unclear whether the developmental abnormalities are caused by a defective AtHD1 or related homologs and are heritable in selfing progeny. We isolated a stable antisense AtHD1 (CASH) transgenic line and a T-DNA insertion line in exon 2 of AtHD1, resulting in a null allele (athd1-t1). Both athd1-t1 and CASH lines display increased levels of histone acetylation and similar developmental abnormalities, which are heritable in the presence of antisense AtHD1 or in the progeny of homozygous (athd1-t1/athd1-t1) plants. Furthermore, when the athd1-t1/athd1-t1 plants are crossed to wild-type plants, the pleiotropic developmental abnormalities are immediately restored in the F1 hybrids, which correlates with AtHD1 expression and reduction of histone H4 Lys12 acetylation. Unlike the situation with the stable code of DNA and histone methylation, developmental changes induced by histone deacetylase defects are immediately reversible, probably through the restoration of a reversible histone acetylation code needed for the normal control of gene regulation and development.


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